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Systematic Review

A Systematic Review on the Therapeutic Potentiality of PD-L1-Inhibiting MicroRNAs for Triple-Negative Breast Cancer: Toward Single-Cell Sequencing-Guided Biomimetic Delivery

1
Research Center for Evidence-Based Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz 5166614766, Iran
2
Immunology Research Center, Tabriz University of Medical Sciences, Tabriz 5165665811, Iran
3
Student Research Committee, Tabriz University of Medical Sciences, Tabriz 5165665811, Iran
4
Medical Oncology Unit, IRCCS Istituto Tumori Giovanni Paolo II, 70124 Bari, Italy
5
Laboratory of Experimental Pharmacology, IRCCS Istituto Tumori Giovanni Paolo II, 70124 Bari, Italy
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Department of Biomedical Sciences and Human Oncology, Unit of Internal Medicine and Clinical Oncology, University of Bari “Aldo Moro”, 70124 Bari, Italy
7
Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz 5166614766, Iran
*
Authors to whom correspondence should be addressed.
These authors jointly supervised this work.
Academic Editor: Paolo Cinelli
Genes 2021, 12(8), 1206; https://doi.org/10.3390/genes12081206
Received: 7 March 2021 / Revised: 28 July 2021 / Accepted: 30 July 2021 / Published: 4 August 2021
(This article belongs to the Special Issue Transcription Factors in Cancer Progression)
The programmed death-ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) is a well-established inhibitory immune checkpoint axis in triple-negative breast cancer (TNBC). Growing evidence indicates that tumoral PD-L1 can lead to TNBC development. Although conventional immune checkpoint inhibitors have improved TNBC patients’ prognosis, their effect is mainly focused on improving anti-tumoral immune responses without substantially regulating oncogenic signaling pathways in tumoral cells. Moreover, the conventional immune checkpoint inhibitors cannot impede the de novo expression of oncoproteins, like PD-L1, in tumoral cells. Accumulating evidence has indicated that the restoration of specific microRNAs (miRs) can downregulate tumoral PD-L1 and inhibit TNBC development. Since miRs can target multiple mRNAs, miR-based gene therapy can be an appealing approach to inhibit the de novo expression of oncoproteins, like PD-L1, restore anti-tumoral immune responses, and regulate various intracellular singling pathways in TNBC. Therefore, we conducted the current systematic review based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) to provide a comprehensive and unbiased synthesis of currently available evidence regarding the effect of PD-L1-inhibiting miRs restoration on TNBC development and tumor microenvironment. For this purpose, we systematically searched the Cochrane Library, Embase, Scopus, PubMed, ProQuest, Web of Science, Ovid, and IranDoc databases to obtain the relevant peer-reviewed studies published before 25 May 2021. Based on the current evidence, the restoration of miR-424-5p, miR-138-5p, miR-570-3p, miR-200c-3p, miR-383-5p, miR-34a-5p, miR-3609, miR-195-5p, and miR-497-5p can inhibit tumoral PD-L1 expression, transform immunosuppressive tumor microenvironment into the pro-inflammatory tumor microenvironment, inhibit tumor proliferation, suppress tumor migration, enhance chemosensitivity of tumoral cells, stimulate tumor apoptosis, arrest cell cycle, repress the clonogenicity of tumoral cells, and regulate various oncogenic signaling pathways in TNBC cells. Concerning the biocompatibility of biomimetic carriers and the valuable insights provided by the single-cell sequencing technologies, single-cell sequencing-guided biomimetic delivery of these PD-L1-inhibiting miRs can decrease the toxicity of traditional approaches, increase the specificity of miR-delivery, enhance the efficacy of miR delivery, and provide the affected patients with personalized cancer therapy. View Full-Text
Keywords: programmed death-ligand 1; PD-L1; triple-negative breast cancer; TNBC; microRNA; microRNA-based gene-therapy; biomimetic carriers; leukosomes; single-cell sequencing; personalized medicine programmed death-ligand 1; PD-L1; triple-negative breast cancer; TNBC; microRNA; microRNA-based gene-therapy; biomimetic carriers; leukosomes; single-cell sequencing; personalized medicine
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MDPI and ACS Style

Shadbad, M.A.; Safaei, S.; Brunetti, O.; Derakhshani, A.; Lotfinejad, P.; Mokhtarzadeh, A.; Hemmat, N.; Racanelli, V.; Solimando, A.G.; Argentiero, A.; Silvestris, N.; Baradaran, B. A Systematic Review on the Therapeutic Potentiality of PD-L1-Inhibiting MicroRNAs for Triple-Negative Breast Cancer: Toward Single-Cell Sequencing-Guided Biomimetic Delivery. Genes 2021, 12, 1206. https://doi.org/10.3390/genes12081206

AMA Style

Shadbad MA, Safaei S, Brunetti O, Derakhshani A, Lotfinejad P, Mokhtarzadeh A, Hemmat N, Racanelli V, Solimando AG, Argentiero A, Silvestris N, Baradaran B. A Systematic Review on the Therapeutic Potentiality of PD-L1-Inhibiting MicroRNAs for Triple-Negative Breast Cancer: Toward Single-Cell Sequencing-Guided Biomimetic Delivery. Genes. 2021; 12(8):1206. https://doi.org/10.3390/genes12081206

Chicago/Turabian Style

Shadbad, Mahdi A., Sahar Safaei, Oronzo Brunetti, Afshin Derakhshani, Parisa Lotfinejad, Ahad Mokhtarzadeh, Nima Hemmat, Vito Racanelli, Antonio G. Solimando, Antonella Argentiero, Nicola Silvestris, and Behzad Baradaran. 2021. "A Systematic Review on the Therapeutic Potentiality of PD-L1-Inhibiting MicroRNAs for Triple-Negative Breast Cancer: Toward Single-Cell Sequencing-Guided Biomimetic Delivery" Genes 12, no. 8: 1206. https://doi.org/10.3390/genes12081206

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